Distinct effects of CGRP on typical and atypical smooth muscle cells involved in generating spontaneous contractions in the mouse renal pelvis
Background and purpose: We investigated the cellular mechanisms underlying spontaneous contractions in the mouse renal pelvis, regulated by calcitonin gene‐related peptide (CGRP). Experimental approach: Spontaneous contractions, action potentials and Ca2+ transients in typical and atypical smooth...
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| Veröffentlicht in: | British journal of pharmacology 2009-12, Vol.158 (8), p.2030-2045 |
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| creator | Hashitani, Hikaru Lang, Richard J Mitsui, Retsu Mabuchi, Yoshio Suzuki, Hikaru |
| description | Background and purpose: We investigated the cellular mechanisms underlying spontaneous contractions in the mouse renal pelvis, regulated by calcitonin gene‐related peptide (CGRP).
Experimental approach: Spontaneous contractions, action potentials and Ca2+ transients in typical and atypical smooth muscle cells (TSMCs and ATSMCs) within the renal pelvis wall were recorded separately using tension and intracellular microelectrode recording techniques and Fluo‐4 Ca2+ imaging. Immunohistochemical and electron microscopic studies were also carried out.
Key results: Bundles of CGRP containing transient receptor potential cation channel, subfamily V, member 1‐positive sensory nerves were situated near both TSMCs and ATSMCs. Nerve stimulation reduced the frequency but augmented the amplitude and duration of spontaneous phasic contractions, action potentials and Ca2+ transients in TSMCs. CGRP and agents increasing internal cyclic adenosine monophosphate (cAMP) mimicked the nerve‐mediated modulation of TSMC activity and suppressed ATSMCs Ca2+ transients. Membrane hyperpolarization induced by CGRP or cAMP stimulators was blocked by glibenclamide, while their negative chronotropic effects were less affected. Glibenclamide enhanced TSMC Ca2+ transients but inhibited ATSMC Ca2+ transients, while both 5‐hydroxydecanoate and diazoxide, a blocker and opener of mitochondrial ATP‐sensitive K+ channels, respectively, reduced the Ca2+ transient frequency in both TSMCs and ATSMCs. Inhibition of mitochondrial function blocked ATSMCs Ca2+ transients and inhibited spontaneous excitation of TSMCs.
Conclusions and implications: The negative chronotropic effects of CGRP result primarily from suppression of ATSMC Ca2+ transients rather than opening of plasmalemmal ATP‐sensitive K+ channels in TSMCs. The positive inotropic effects of CGRP may derive from activation of TSMC L‐type Ca2+ channels. Mitochondrial Ca2+ handling in ATSMCs also plays a critical role in generating Ca2+ transients. |
| doi_str_mv | 10.1111/j.1476-5381.2009.00514.x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2807665</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>745631330</sourcerecordid><originalsourceid>FETCH-LOGICAL-c5704-b4600a5b3a1e30d27840f551645bcb967f4f7b82e71db11dc49f12d42e15e83a3</originalsourceid><addsrcrecordid>eNqNUV1v0zAUtRCIlcFfQH7jqdl1bMeJhJCgsA1pEhOCZ8txblpXiR3itFv_BL8Zh24VPIFffKzzoXt9CKEMMpbOxTZjQhVLyUuW5QBVBiCZyO6fkMWJeEoWAKCWjJXlGXkR4xYgkUo-J2fJI4FVYkF-fnRxct5OFNsW7RRpaOnq6ustDZ5Oh8FZ01HjG2oeH7EPYdrQfhdth9Ri10Xq_D50e2wSoGv0OJqUuaZxCH4yHsMuUpvgaOzkgp_1dNog7ROBdESfYgfs9i6-JM9a00V89XCfk--Xn76trpc3X64-r97fLK1UIJa1KACMrLlhyKHJVSmglZIVQta2rgrVilbVZY6KNTVjjRVVy_JG5Mgkltzwc_LumDvs6h4bi_NwnR5G15vxoINx-m_Gu41eh73OS1BFIVPAm4eAMfzYYZx07-L8Gcd1tRKy4Ixz-LeS86KqWDkry6PSjiHGEdvTPAz03Lve6rlePder59717971fbK-_nOfk_Gx6CR4exTcuQ4P_x2sP9xeJ8B_Af2zv0Y</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>733699180</pqid></control><display><type>article</type><title>Distinct effects of CGRP on typical and atypical smooth muscle cells involved in generating spontaneous contractions in the mouse renal pelvis</title><source>Wiley Online Library - AutoHoldings Journals</source><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Wiley Free Content</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Hashitani, Hikaru ; Lang, Richard J ; Mitsui, Retsu ; Mabuchi, Yoshio ; Suzuki, Hikaru</creator><creatorcontrib>Hashitani, Hikaru ; Lang, Richard J ; Mitsui, Retsu ; Mabuchi, Yoshio ; Suzuki, Hikaru</creatorcontrib><description>Background and purpose: We investigated the cellular mechanisms underlying spontaneous contractions in the mouse renal pelvis, regulated by calcitonin gene‐related peptide (CGRP).
Experimental approach: Spontaneous contractions, action potentials and Ca2+ transients in typical and atypical smooth muscle cells (TSMCs and ATSMCs) within the renal pelvis wall were recorded separately using tension and intracellular microelectrode recording techniques and Fluo‐4 Ca2+ imaging. Immunohistochemical and electron microscopic studies were also carried out.
Key results: Bundles of CGRP containing transient receptor potential cation channel, subfamily V, member 1‐positive sensory nerves were situated near both TSMCs and ATSMCs. Nerve stimulation reduced the frequency but augmented the amplitude and duration of spontaneous phasic contractions, action potentials and Ca2+ transients in TSMCs. CGRP and agents increasing internal cyclic adenosine monophosphate (cAMP) mimicked the nerve‐mediated modulation of TSMC activity and suppressed ATSMCs Ca2+ transients. Membrane hyperpolarization induced by CGRP or cAMP stimulators was blocked by glibenclamide, while their negative chronotropic effects were less affected. Glibenclamide enhanced TSMC Ca2+ transients but inhibited ATSMC Ca2+ transients, while both 5‐hydroxydecanoate and diazoxide, a blocker and opener of mitochondrial ATP‐sensitive K+ channels, respectively, reduced the Ca2+ transient frequency in both TSMCs and ATSMCs. Inhibition of mitochondrial function blocked ATSMCs Ca2+ transients and inhibited spontaneous excitation of TSMCs.
Conclusions and implications: The negative chronotropic effects of CGRP result primarily from suppression of ATSMC Ca2+ transients rather than opening of plasmalemmal ATP‐sensitive K+ channels in TSMCs. The positive inotropic effects of CGRP may derive from activation of TSMC L‐type Ca2+ channels. Mitochondrial Ca2+ handling in ATSMCs also plays a critical role in generating Ca2+ transients.</description><identifier>ISSN: 0007-1188</identifier><identifier>EISSN: 1476-5381</identifier><identifier>DOI: 10.1111/j.1476-5381.2009.00514.x</identifier><identifier>PMID: 20050194</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Action Potentials - drug effects ; Animals ; ATP‐sensitive K+ (KATP) channels ; Calcitonin Gene-Related Peptide - pharmacology ; Calcium - metabolism ; Calcium Channels, L-Type - drug effects ; Calcium Channels, L-Type - metabolism ; CGRP ; Humans ; Immunohistochemistry ; intracellular calcium ; KATP Channels - metabolism ; Kidney Pelvis - cytology ; Kidney Pelvis - drug effects ; Kidney Pelvis - metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Microelectrodes ; Microscopy, Electron ; mitochondria ; Mitochondria - metabolism ; Muscle Contraction - drug effects ; Myocytes, Smooth Muscle - drug effects ; Myocytes, Smooth Muscle - metabolism ; renal pelvis ; Research Papers ; sensory nerve ; smooth muscle</subject><ispartof>British journal of pharmacology, 2009-12, Vol.158 (8), p.2030-2045</ispartof><rights>2009 The Authors. Journal compilation © 2009 The British Pharmacological Society</rights><rights>Journal compilation © 2009 The British Pharmacological Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5704-b4600a5b3a1e30d27840f551645bcb967f4f7b82e71db11dc49f12d42e15e83a3</citedby><cites>FETCH-LOGICAL-c5704-b4600a5b3a1e30d27840f551645bcb967f4f7b82e71db11dc49f12d42e15e83a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807665/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2807665/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,725,778,782,883,1414,1430,27907,27908,45557,45558,46392,46816,53774,53776</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20050194$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hashitani, Hikaru</creatorcontrib><creatorcontrib>Lang, Richard J</creatorcontrib><creatorcontrib>Mitsui, Retsu</creatorcontrib><creatorcontrib>Mabuchi, Yoshio</creatorcontrib><creatorcontrib>Suzuki, Hikaru</creatorcontrib><title>Distinct effects of CGRP on typical and atypical smooth muscle cells involved in generating spontaneous contractions in the mouse renal pelvis</title><title>British journal of pharmacology</title><addtitle>Br J Pharmacol</addtitle><description>Background and purpose: We investigated the cellular mechanisms underlying spontaneous contractions in the mouse renal pelvis, regulated by calcitonin gene‐related peptide (CGRP).
Experimental approach: Spontaneous contractions, action potentials and Ca2+ transients in typical and atypical smooth muscle cells (TSMCs and ATSMCs) within the renal pelvis wall were recorded separately using tension and intracellular microelectrode recording techniques and Fluo‐4 Ca2+ imaging. Immunohistochemical and electron microscopic studies were also carried out.
Key results: Bundles of CGRP containing transient receptor potential cation channel, subfamily V, member 1‐positive sensory nerves were situated near both TSMCs and ATSMCs. Nerve stimulation reduced the frequency but augmented the amplitude and duration of spontaneous phasic contractions, action potentials and Ca2+ transients in TSMCs. CGRP and agents increasing internal cyclic adenosine monophosphate (cAMP) mimicked the nerve‐mediated modulation of TSMC activity and suppressed ATSMCs Ca2+ transients. Membrane hyperpolarization induced by CGRP or cAMP stimulators was blocked by glibenclamide, while their negative chronotropic effects were less affected. Glibenclamide enhanced TSMC Ca2+ transients but inhibited ATSMC Ca2+ transients, while both 5‐hydroxydecanoate and diazoxide, a blocker and opener of mitochondrial ATP‐sensitive K+ channels, respectively, reduced the Ca2+ transient frequency in both TSMCs and ATSMCs. Inhibition of mitochondrial function blocked ATSMCs Ca2+ transients and inhibited spontaneous excitation of TSMCs.
Conclusions and implications: The negative chronotropic effects of CGRP result primarily from suppression of ATSMC Ca2+ transients rather than opening of plasmalemmal ATP‐sensitive K+ channels in TSMCs. The positive inotropic effects of CGRP may derive from activation of TSMC L‐type Ca2+ channels. Mitochondrial Ca2+ handling in ATSMCs also plays a critical role in generating Ca2+ transients.</description><subject>Action Potentials - drug effects</subject><subject>Animals</subject><subject>ATP‐sensitive K+ (KATP) channels</subject><subject>Calcitonin Gene-Related Peptide - pharmacology</subject><subject>Calcium - metabolism</subject><subject>Calcium Channels, L-Type - drug effects</subject><subject>Calcium Channels, L-Type - metabolism</subject><subject>CGRP</subject><subject>Humans</subject><subject>Immunohistochemistry</subject><subject>intracellular calcium</subject><subject>KATP Channels - metabolism</subject><subject>Kidney Pelvis - cytology</subject><subject>Kidney Pelvis - drug effects</subject><subject>Kidney Pelvis - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Microelectrodes</subject><subject>Microscopy, Electron</subject><subject>mitochondria</subject><subject>Mitochondria - metabolism</subject><subject>Muscle Contraction - drug effects</subject><subject>Myocytes, Smooth Muscle - drug effects</subject><subject>Myocytes, Smooth Muscle - metabolism</subject><subject>renal pelvis</subject><subject>Research Papers</subject><subject>sensory nerve</subject><subject>smooth muscle</subject><issn>0007-1188</issn><issn>1476-5381</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUV1v0zAUtRCIlcFfQH7jqdl1bMeJhJCgsA1pEhOCZ8txblpXiR3itFv_BL8Zh24VPIFffKzzoXt9CKEMMpbOxTZjQhVLyUuW5QBVBiCZyO6fkMWJeEoWAKCWjJXlGXkR4xYgkUo-J2fJI4FVYkF-fnRxct5OFNsW7RRpaOnq6ustDZ5Oh8FZ01HjG2oeH7EPYdrQfhdth9Ri10Xq_D50e2wSoGv0OJqUuaZxCH4yHsMuUpvgaOzkgp_1dNog7ROBdESfYgfs9i6-JM9a00V89XCfk--Xn76trpc3X64-r97fLK1UIJa1KACMrLlhyKHJVSmglZIVQta2rgrVilbVZY6KNTVjjRVVy_JG5Mgkltzwc_LumDvs6h4bi_NwnR5G15vxoINx-m_Gu41eh73OS1BFIVPAm4eAMfzYYZx07-L8Gcd1tRKy4Ixz-LeS86KqWDkry6PSjiHGEdvTPAz03Lve6rlePder59717971fbK-_nOfk_Gx6CR4exTcuQ4P_x2sP9xeJ8B_Af2zv0Y</recordid><startdate>200912</startdate><enddate>200912</enddate><creator>Hashitani, Hikaru</creator><creator>Lang, Richard J</creator><creator>Mitsui, Retsu</creator><creator>Mabuchi, Yoshio</creator><creator>Suzuki, Hikaru</creator><general>Blackwell Publishing Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7QP</scope><scope>5PM</scope></search><sort><creationdate>200912</creationdate><title>Distinct effects of CGRP on typical and atypical smooth muscle cells involved in generating spontaneous contractions in the mouse renal pelvis</title><author>Hashitani, Hikaru ; Lang, Richard J ; Mitsui, Retsu ; Mabuchi, Yoshio ; Suzuki, Hikaru</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5704-b4600a5b3a1e30d27840f551645bcb967f4f7b82e71db11dc49f12d42e15e83a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Action Potentials - drug effects</topic><topic>Animals</topic><topic>ATP‐sensitive K+ (KATP) channels</topic><topic>Calcitonin Gene-Related Peptide - pharmacology</topic><topic>Calcium - metabolism</topic><topic>Calcium Channels, L-Type - drug effects</topic><topic>Calcium Channels, L-Type - metabolism</topic><topic>CGRP</topic><topic>Humans</topic><topic>Immunohistochemistry</topic><topic>intracellular calcium</topic><topic>KATP Channels - metabolism</topic><topic>Kidney Pelvis - cytology</topic><topic>Kidney Pelvis - drug effects</topic><topic>Kidney Pelvis - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Microelectrodes</topic><topic>Microscopy, Electron</topic><topic>mitochondria</topic><topic>Mitochondria - metabolism</topic><topic>Muscle Contraction - drug effects</topic><topic>Myocytes, Smooth Muscle - drug effects</topic><topic>Myocytes, Smooth Muscle - metabolism</topic><topic>renal pelvis</topic><topic>Research Papers</topic><topic>sensory nerve</topic><topic>smooth muscle</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hashitani, Hikaru</creatorcontrib><creatorcontrib>Lang, Richard J</creatorcontrib><creatorcontrib>Mitsui, Retsu</creatorcontrib><creatorcontrib>Mabuchi, Yoshio</creatorcontrib><creatorcontrib>Suzuki, Hikaru</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>British journal of pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hashitani, Hikaru</au><au>Lang, Richard J</au><au>Mitsui, Retsu</au><au>Mabuchi, Yoshio</au><au>Suzuki, Hikaru</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Distinct effects of CGRP on typical and atypical smooth muscle cells involved in generating spontaneous contractions in the mouse renal pelvis</atitle><jtitle>British journal of pharmacology</jtitle><addtitle>Br J Pharmacol</addtitle><date>2009-12</date><risdate>2009</risdate><volume>158</volume><issue>8</issue><spage>2030</spage><epage>2045</epage><pages>2030-2045</pages><issn>0007-1188</issn><eissn>1476-5381</eissn><abstract>Background and purpose: We investigated the cellular mechanisms underlying spontaneous contractions in the mouse renal pelvis, regulated by calcitonin gene‐related peptide (CGRP).
Experimental approach: Spontaneous contractions, action potentials and Ca2+ transients in typical and atypical smooth muscle cells (TSMCs and ATSMCs) within the renal pelvis wall were recorded separately using tension and intracellular microelectrode recording techniques and Fluo‐4 Ca2+ imaging. Immunohistochemical and electron microscopic studies were also carried out.
Key results: Bundles of CGRP containing transient receptor potential cation channel, subfamily V, member 1‐positive sensory nerves were situated near both TSMCs and ATSMCs. Nerve stimulation reduced the frequency but augmented the amplitude and duration of spontaneous phasic contractions, action potentials and Ca2+ transients in TSMCs. CGRP and agents increasing internal cyclic adenosine monophosphate (cAMP) mimicked the nerve‐mediated modulation of TSMC activity and suppressed ATSMCs Ca2+ transients. Membrane hyperpolarization induced by CGRP or cAMP stimulators was blocked by glibenclamide, while their negative chronotropic effects were less affected. Glibenclamide enhanced TSMC Ca2+ transients but inhibited ATSMC Ca2+ transients, while both 5‐hydroxydecanoate and diazoxide, a blocker and opener of mitochondrial ATP‐sensitive K+ channels, respectively, reduced the Ca2+ transient frequency in both TSMCs and ATSMCs. Inhibition of mitochondrial function blocked ATSMCs Ca2+ transients and inhibited spontaneous excitation of TSMCs.
Conclusions and implications: The negative chronotropic effects of CGRP result primarily from suppression of ATSMC Ca2+ transients rather than opening of plasmalemmal ATP‐sensitive K+ channels in TSMCs. The positive inotropic effects of CGRP may derive from activation of TSMC L‐type Ca2+ channels. Mitochondrial Ca2+ handling in ATSMCs also plays a critical role in generating Ca2+ transients.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>20050194</pmid><doi>10.1111/j.1476-5381.2009.00514.x</doi><tpages>16</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Action Potentials - drug effects Animals ATP‐sensitive K+ (KATP) channels Calcitonin Gene-Related Peptide - pharmacology Calcium - metabolism Calcium Channels, L-Type - drug effects Calcium Channels, L-Type - metabolism CGRP Humans Immunohistochemistry intracellular calcium KATP Channels - metabolism Kidney Pelvis - cytology Kidney Pelvis - drug effects Kidney Pelvis - metabolism Male Mice Mice, Inbred BALB C Microelectrodes Microscopy, Electron mitochondria Mitochondria - metabolism Muscle Contraction - drug effects Myocytes, Smooth Muscle - drug effects Myocytes, Smooth Muscle - metabolism renal pelvis Research Papers sensory nerve smooth muscle |
| title | Distinct effects of CGRP on typical and atypical smooth muscle cells involved in generating spontaneous contractions in the mouse renal pelvis |
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